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P Danielian

Publications and source records attributed to P Danielian.

10 recordsLinked to original sources
PubMed2004

A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at term.

OBJECTIVE: To compare the efficacy of 100 microg of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction. DESIGN: A non-blinded, randomised, controlled trial. SETTING: A tertiary level, teaching Scottish Hospital. POPULATION: Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8. METHODS: The women were randomly allocated to receive either 100 microg of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol). MAIN OUTCOME MEASURE: The number delivering vaginally within 24 hours of the induction. RESULTS: Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a pound 1100 saving on direct drug costs in the misoprostol group. CONCLUSIONS: Oral misoprostol (100 microg) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction.

Administration, Intravaginal↗
PubMed2002

Active management of term prelabour rupture of membranes with oral misoprostol.

OBJECTIVE: To compare the active management of term prelabour rupture of membranes with oral misoprostol with conservative management for 24 hours followed by induction with oxytocin or prostaglandin E(2) (PGE(2)) gel. DESIGN: A non-blinded randomised controlled trial. SETTING: Induction and labour wards, Aberdeen Maternity Hospital. POPULATION: Sixty-one women with confirmed prelabour rupture of the membranes at > or =36 weeks of gestation. METHODS: The women were randomised to 50 microg of oral misoprostol repeated every 4 hours, if required, to a maximum of five doses (active group), or to induction of labour with PGE(2) gel or oxytocin only if not in spontaneous labour 24 hours after prelabour rupture of membranes (conservative group). MAIN OUTCOME MEASURES: Number of women in active labour within 24 hours of the prelabour rupture of membranes, preference of women for any one particular method of management in any subsequent pregnancy with prelabour rupture of membranes. RESULTS: 93.3% of the active group and 54.8% of the conservative group were in spontaneous labour within 24 hours of the prelabour rupture of membranes (RR 1.7, 95% CI 1.2 to 2.4). Of those achieving a vaginal delivery, 72% of the active group did so within 24 hours of the prelabour rupture of membranes as compared with 26.9% of the conservative group (RR 2.7, 95% CI 1.4 to 5.3, P = 0.002). There were no significant differences in the neonatal or maternal outcomes. In the active group, 78% felt they would have the same method of induction as compared with 40% in the conservative group (RR 1.9, 95% CI 1.1 to 3.3, P = 0.03). CONCLUSIONS: Active management with oral misoprostol resulted in more women going into labour and delivering within 24 hours of the prelabour rupture of membranes with no increase in maternal or neonatal complications. Women tended to view active management of prelabour rupture of membranes more positively. Oral misoprostol might be an option to consider in those wishing active management.

Administration, Oral↗
PubMed2001

A comparison of oral and vaginal misoprostol tablets in induction of labour at term.

OBJECTIVE: To compare the efficacy of equivalent doses of orally administered with vaginally administered misoprostol in induction of labour at term. DESIGN: A non-blinded randomised controlled trial. SETTING: Induction and labour wards of a UK teaching hospital. PARTICIPANTS: Two hundred and forty-five pregnant women at term, with medical or obstetric indications for labour induction and unfavourable cervices. METHODS: The women were randomly assigned to receive 50 microgm of misoprostol orally or vaginally four hourly to a maximum of five doses. MAIN OUTCOME MEASURES: Interval from induction to vaginal delivery, mode of delivery, oxytocic and analgesic requirements in labour, neonatal outcome, patient satisfaction and acceptability. RESULTS: The mean induction to vaginal delivery interval was significantly shorter in the vaginal group compared with the oral group (17.8h vs 27.9h: mean difference 10.1 hrs, 95% CI 5.8-14.4). More women were delivered within 24 hours (80% vs 46.3%; RR 1.7, 95% CI 1.3-2.1) and fewer women needed oxytocin augmentation (39% vs 58.2%; RR 0.67, 95% CI 0.5-0.9) in the vaginal group. There was no difference in the mode of delivery, analgesic requirements or neonatal outcomes in the two groups. There was a higher incidence of uterine hyperstimulation in the vaginal group (4.9% vs 0.8%, RR 6, 95% CI 0.07-48.7) and more caesarean sections were performed for fetal distress in this group (13% Vs 2.4%, RR 5.3, 95% CI 1.6-17.7), although the overall operative delivery rate was similar in the two groups. CONCLUSION: Misoprostol effectively induces labour, with the vaginal route of administration having a faster action than the oral route in equivalent doses. However, the more frequent occurrence of hyperstimulation and the higher intervention rate for fetal distress in the vaginal group could mean that the preferred route might be oral. More trials are needed to find the right oral dosage that combines efficacy with safety.

Administration, Intravaginal↗
PubMed1999

Misoprostol for induction of labour at term: a more effective agent than dinoprostone vaginal gel.

OBJECTIVE: To compare the efficacy of vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term. DESIGN: A single-blind randomised comparative trial. SETTING: Induction and labour wards of a UK teaching hospital. PARTICIPANTS: Two hundred and eleven pregnant women at term in whom induction of labour was indicated, and with no contra-indication to the use of prostaglandins for the induction of labour. INTERVENTION: The women were randomly assigned to receive vaginal administration of either misoprostol 50 microg four hourly (to a maximum of four doses) or dinoprostone gel 1 mg six hourly (to a maximum of three doses). MAIN OUTCOME MEASURES: Time from induction to delivery, oxytocin requirement in labour, analgesic requirement, mode of delivery, neonatal outcome. RESULTS: The misoprostol group had a highly significant reduction in median induction-delivery interval compared with the dinoprostone group (14.4 hours vs 22.9 hours; P < 0.00001). In addition, more women delivered after only one dose (77% vs 49%; P < 0.0001, OR 3.51, 95% CI 1.94-6.35), and within 12 and 24 hours. There was a reduced need for oxytocin augmentation in labour (21% vs 47%; P < 0.0001, OR 0.30, 95% CI 0.16-0.54). There was no difference in analgesia requirement in labour, or in mode of delivery. There were no adverse neonatal outcomes associated with the use of misoprostol. Women in the misoprostol group experienced more pain in the interval between induction and being given analgesia in labour, but this did not reach statistical significance. CONCLUSIONS: Misoprostol 50 microg vaginally is a more effective induction agent than 1 mg dinoprostone vaginal gel, with no apparent adverse effects on mode of delivery, or on the fetus. The higher pain scores in the misoprostol group must be balanced against the reduction in time spent having labour induced, and the reduction in need for intravenous oxytocin augmentation. Further randomised studies must continue to exclude the possibility of rare adverse side effects.

Adolescent↗
PubMed1994

Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions.

We have used a series of human estrogen receptor (ER) mutants to evaluate the cell- and promoter-specific transcriptional activities of the TAF1 and TAF2 transactivation regions within the human ER. We show that the manifestation of TAF1 or TAF2 function depends strongly upon promoter context; on certain promoters, both the TAF1 and TAF2 activators are required for wild-type transcriptional activity, whereas on other promoters, the TAF1 and TAF2 activators function independently. Using these constructs, we show that the antagonist activity of the triphenylethylene-derived antiestrogens, e.g. tamoxifen, arises from their intrinsic inability to activate ER TAF2 function. However, on certain promoters, these antiestrogens efficiently activate gene transcription through ER. Consistent with this observation, the TAF2 function of the ER is not required on all promoters. In these TAF2-independent promoter contexts, TAF2 function may be provided by a separate transcription factor bound to the promoter. These data suggest that 1) TAF1 may be the major transcriptional activator of the ER; and 2) TAF2 functions as a transcriptional facilitator. On promoters where TAF2 function is provided independently of the ER, the TAF1 function of the ER can function independently of TAF2 activity, allowing triphenylethylene-derived antiestrogens to demonstrate partial agonist activity. These observations provide a possible molecular explanation for the tissue-specific partial agonist properties of tamoxifen and related triphenylethylene antiestrogens observed in vivo.

Binding, Competitive↗
PubMed1993

Structure and function of the estrogen receptor.

The hormone binding domain of the estrogen receptor is required not only for binding estradiol but also to form stable homodimers of the protein and mediate transcriptional activation by the receptor. Residues that are essential for estrogen binding are also involved in dimerization, suggesting that the hormone-binding pocket is at or near the dimer interface. Distinct hydrophobic and charged residues are essential for hormone-dependent transcriptional activation, and these appear to be conserved by other members of the nuclear receptor family. We have found that the pure antiestrogens ICI 164384 and ICI 182780 increase the turnover of the receptor compared with that in the presence of estradiol. Because it is likely that the pure antiestrogens bind to a similar region of the receptor as that of estradiol, we propose that they inhibit receptor dimerization by means of their 7 alpha alkyl-amide extension. It appears that as a consequence nuclear uptake is inhibited and the receptor more rapidly degraded in the cytoplasm.

Animals↗